Hyperhomocysteinemia in pediatric β-thalassemia: links to vitamin cofactor deficiencies and oxidative stress.

Abstract

Background: Homocysteine metabolism is crucial to maintaining vascular and metabolic homeostasis, yet its dysregulation in pediatric β-thalassemia major (β-TM) remains poorly understood.

Purpose: This study investigated the prevalence and determinants of hyperhomocysteinemia in pediatric β-TM with a focus on vitamin B9 (folate), B12, and B6 deficiencies, oxidative stress marker levels, and the impact of splenectomy.

Methods: A cross-sectional study was conducted of 92 pediatric β-TM patients. Levels of plasma homocysteine, vitamins B9, B12, and B6, and oxidative stress marker (protein carbonyls, thiols, nitrotyrosine, and nitric oxide metabolites) levels were measured. The patients were grouped based on their splenectomy status. The MTHFR C677T polymorphism was genotyped in a subset of patients (n=39). The statistical analyses included t tests, analysis of variance, Pearson's correlation, and multivariate regression.

Results: Overall, 93% of patients had hyperhomocysteinemia (≥15 μM), with the values of 50% exceeding 30 μM. Homocysteine levels were negatively correlated with folate levels (r=-0.22, P=0.03) and weakly correlated with B12 levels (r=-0.18, P=0.08). Vitamin B6 levels were not significantly associated with homocysteine levels. Post-splenectomy, patients had significantly higher homocysteine levels (43.3 μM vs. 32.3 μM, P=0.002) but lower nitrotyrosine levels (P=0.035), suggesting reduced nitrative stress. The MTHFR C677T genotype did not significantly influence homocysteine levels in our cohort.

Conclusion: Hyperhomocysteinemia is prevalent in pediatric β-TM, driven primarily by severe folate and B12 deficiencies. Splenectomy exacerbates hyperhomocysteinemia but reduces nitrative stress, indicating complex metabolic shifts postsplenectomy. These findings highlight the need for routine homocysteine monitoring and targeted vitamin supplementation to mitigate the potential vascular risks of pediatric thalassemia.